We continued our study of the V3 loop of the HIV-1 envelope glycoprotein gp120. Experimental restraints derived from liquid- and solid-state NMR data were used, and simulated annealing was performed using the XPLOR program. We published a second paper. We continued to develop Monte Carlo simulation techniques in the CHARMM program, using biased searching of main-chain and side-chain dihedral conformations. Soft-core potentials were implemented and tested. Generalized Born and finite-difference Poisson-Boltzmann solvation models were evaluated. We continued our computational study of trimethoprim resistance in dihydrofolate reductase (DHFR) from Streptococcus pneumonia. Monte Carlo simulations were performed on a homology model of DHFR with the antibiotic trimethoprim bound. The structural effects of mutating Ile 100 to Leu or Met were investigated. Simulations suggested that the mutation Ile100Leu results in main-chain relaxation that breaks a hydrogen bond between residue 100 and trimethoprim and thus confers resistance to trimethoprim. A manuscript is in preparation. We made a homology model of an omega-crystallin from scallop, based on the crystal structure of human aldehyde dehydrogenase (ALDH2). Experiments and computer modeling were used to probe the function of this protein. A paper is in press. We modeled the binding mode of substrate 3,4-dihydroxyphenylglycolaldehyde (DHMAL) and its derivatives at the active site of aldose reductase utilizing CHARMM. This modeling provided a structural basis for the reduction of DHMAL by aldose reductase. In particular, we pointed out the importance of the 2'-hydroxl group of DHMAL during catalysis. A manuscript is in preparation. We are in the process of elucidating the catalytic mechanism of Serotonin N-acetyltransferase utilizing combined potentials of quantum mechanics and molecular mechanics (GAMESS/CHARMM).